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Investigators from the Consejo Superior de Investigaciones Científicas (CSIC) and the University of Las Palmas de Gran Canaria and California (USA) have discovered a molecular mechanism involved in the development of autoimmune diseases like lupus. These are the receptors LXR (Liver X Receptors) that regulate the removal of the remains of dead cells by apoptosis, a process that, when it fails, it causes inflammation of surrounding tissue and the body's immune response. The research, conducted with mice, opens the door to the use of these receptors as therapeutic targets for these diseases.

Antonio Castrillo, CSIC researcher at the Institute for Biomedical Research (Joint CSIC and Universidad Autónoma de Madrid) and director of research, explains: "The research in mice has shown that in the absence of these receptors, the process of removal of dead cells is severely compromised. "According to the research, these receptors, proteins residing in the cell nucleus and known so far for its role in cholesterol metabolism, regulate the expression of an important gene involved in removal of cellular debris.

Indeed, mice lacking LXR were dead cellular debris deposited in many tissues. In addition, developed a chronic inflammatory syndrome whose symptoms were similar to those of systemic lupus erythematosus, an autoimmune disease in humans that causes chronic inflammation of the tissues and in 90% of cases affecting women. "Although the causes of lupus are not known and probably multiple, there is evidence showing that these patients have cellular debris in blood and dead tissue, similar to those observed in these mice," explains the scientist of the CSIC.

The researchers also found that these mice by administering a compound that activates the LXR receptor decreased the incidence and severity of the immune disorder, in addition to correcting the presence of dead cells in tissues. "This discovery opens the door to the use of LXR receptor as a possible therapeutic target in the treatment of multiple autoimmune diseases, not only for lupus," concludes the researcher. The research, conducted by researcher at the CSIC Antonio Castrillo, also has the participation of researchers from the University of Las Palmas de Gran Canaria, University of California and the Hospital Materno Infantil de Gran Canaria.

Researchers have explored the apoptosis, a mechanism of programmed cell death that occurs regularly in the body in many pathophysiological situations, such as during the renewal of tissues. Between 50 and 100 trillion cells renew themselves every day for apoptosis in humans. When these cells die, their remains are removed by other specialized cells, phagocytes, and reused by the body. Castrillo explains: "When this process fails, the dead cells can not set aside time to release their cellular contents, causing inflammation in surrounding tissues. It is important to know how the process works and what protein interactions or cellular pathways are involved in cell signaling. "

Furthermore, this continuous release of intracellular elements generates an immune response because the body recognizes them as a threat and generate specific antibodies against them (autoantibodies). The result is an autoimmune disease, caused by the immune system to discharge its defensive arsenal against its own cells and tissues in the body of irreversibly damaging the functioning of vital organs.

Some autoimmune diseases are systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis or thyroiditis. Although its causes are many, the conclusions of this work can serve to develop new therapeutic alternatives based LXR receptor activators that help combat these diseases.